降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡

doi:10.12066/j.issn.1007-2861.2720

上海大学学报(自然科学版) ›› 2026, Vol. 32 ›› Issue (2): 202-211.doi: 10.12066/j.issn.1007-2861.2720

• 特稿 • 上一篇

降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡

毕沈艳¹, 陈灵寒², 喻溥蛟³, 王佳琪², 王丽君², 许嘉鸿³

1. 宁夏医科大学上海市浦东新区公利医院研究生培养基地, 上海 200135;
2. 上海大学生命科学学院, 上海 200444;
3. 上海市浦东新区公利医院心血管内科, 上海 200135

收稿日期:2025-12-08 发布日期:2026-05-11
通讯作者: 许嘉鸿(1969-), 男, 教授, 博士生导师, 博士, 研究方向为心力衰竭的基础与临床. E-mail:jiahongxushu@shu.edu.cn
基金资助:
国家自然科学基金资助项目(82370370, 82400349); 浦东新区卫生健康委员会优秀青年医学人才培养计划资助项目(PWRq-2024-25); 上海市卫生健康系统重点学科资助项目(2024ZDXK0024); 浦东新区卫健委重点学科资助项目(PWZxk2022-15)

Alleviation of cardiomyocyte apoptosis by reducing RNA binding protein FUS and inhibiting circ-ZNF609

BI Shenyan¹, CHEN Linghan², YU Pujiao³, WANG Jiaqi², WANG Lijun², XU Jiahong³

1. Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai 200135, China;
2. School of Life Sciences, Shanghai University, Shanghai 200444, China;
3. Department of Cardiology, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, China

Received:2025-12-08 Published:2026-05-11

摘要/Abstract

摘要： 探究RNA结合蛋白(RNA binding protein,RBP)肉瘤融合(fused in sarcoma,FUS)蛋白调控circ-ZNF609(circBase ID:mmu_circ_0001797)减轻由心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)导致的心肌细胞凋亡.基于生物信息学分析发现,FUS是circ-ZNF609两翼反向互补序列结合的潜在剪接因子.构建I/RI动物模型和氧糖剥夺/恢复(oxygen-glucose deprivation/recovery,OGD/R)细胞模型,通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling,TUNEL)法染色、实时定量逆转录多聚酶链反应(quantitativereverse transcription polymerase chain reaction,qRT-PCR)等方法证明了FUS能调控心肌细胞circ-ZNF609的生物生成,抑制FUS对OGD/R诱导的心肌细胞凋亡的保护作用被circ-ZNF609过表达所逆转.因此,抑制FUS是对抗心肌缺血再灌注损伤病理过程的一种有前景的治疗策略.

关键词: 肉瘤融合(fused in sarcoma, FUS), 环状RNA, circ-ZNF609, 心肌细胞凋亡

Abstract: This paper aims to investigate the regulatory role of RNA binding protein (RBP) fused in sarcoma (FUS) in the mechanism by which circ-ZNF609 (circBase ID: mmu_circ_0001797) alleviates cardiomyocyte apoptosis caused by ischemia/reperfusion injury (I/RI). Bioinformatics analysis revealed that FUS was a potential splicing factor binding to the flanking reverse complementary sequences of circ-ZNF609. Subsequently, an I/RI animal model and an oxygen-glucose deprivation/recovery (OGD/R) cell model were constructed. Methods such as terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to validate that FUS can regulate the biogenesis of circ-ZNF609 in myocardial cells. The protective effect of FUS on OGD/R-induced cardiomyocyte apoptosis is reversed by circ-ZNF609 overexpression. Therefore, inhibiting FUS is a promising therapeutic strategy against the pathological process of myocardial ischemia/reperfusion injury.

Key words: fused in sarcoma (FUS), circular RNA, circ-ZNF609, cardiomyocyte apoptosis

中图分类号:

R541

毕沈艳, 陈灵寒, 喻溥蛟, 王佳琪, 王丽君, 许嘉鸿. 降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡[J]. 上海大学学报(自然科学版), 2026, 32(2): 202-211.

BI Shenyan, CHEN Linghan, YU Pujiao, WANG Jiaqi, WANG Lijun, XU Jiahong. Alleviation of cardiomyocyte apoptosis by reducing RNA binding protein FUS and inhibiting circ-ZNF609[J]. Journal of Shanghai University（Natural Science Edition）, 2026, 32(2): 202-211.

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降低RNA结合蛋白FUS通过抑制circ-ZNF609减轻心肌细胞凋亡

Alleviation of cardiomyocyte apoptosis by reducing RNA binding protein FUS and inhibiting circ-ZNF609

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